title: Adjuvant chemotherapy with gemcitabine and long-term outcomes among patients with resected pancreatic cancer: the CONKO-001 randomized trial.
abstract: OBJECTIVE
  The prognosis for patients with pancreatic cancer is poor, even after resection with curative intent. Gemcitabine-based chemotherapy is standard treatment for advanced pancreatic cancer, but its effect on survival in the adjuvant setting has not been demonstrated.
  
  
  OBJECTIVE
  To analyze whether previously reported improvement in disease-free survival with adjuvant gemcitabine therapy translates into improved overall survival.
  
  
  METHODS
  CONKO-001 (Charité Onkologie 001), a multicenter, open-label, phase 3 randomized trial to evaluate the efficacy and toxicity of gemcitabine in patients with pancreatic cancer after complete tumor resection. Patients with macroscopically completely removed pancreatic cancer entered the study between July 1998 and December 2004 in 88 hospitals in Germany and Austria. Follow-up ended in September 2012.
  
  
  METHODS
  After stratification for tumor stage, nodal status, and resection status, patients were randomly assigned to either adjuvant gemcitabine treatment (1g/m2 d 1, 8, 15, q 4 weeks) for 6 months or to observation alone.
  
  
  METHODS
  The primary end point was disease-free survival. Secondary end points included treatment safety and overall survival, with overall survival defined as the time from date of randomization to death. Patients lost to follow-up were censored on the date of their last follow-up.
  
  
  RESULTS
  A total of 368 patients were randomized, and 354 were eligible for intention-to-treat-analysis. By September 2012, 308 patients (87.0% [95% CI, 83.1%-90.1%]) had relapsed and 316 patients (89.3% [95% CI, 85.6%-92.1%]) had died. The median follow-up time was 136 months. The median disease-free survival was 13.4 (95% CI, 11.6-15.3) months in the treatment group compared with 6.7 (95% CI, 6.0-7.5) months in the observation group (hazard ratio, 0.55 [95% CI, 0.44-0.69]; P < .001). Patients randomized to adjuvant gemcitabine treatment had prolonged overall survival compared with those randomized to observation alone (hazard ratio, 0.76 [95% CI, 0.61-0.95]; P = .01), with 5-year overall survival of 20.7% (95% CI, 14.7%-26.6%) vs 10.4% (95% CI, 5.9%-15.0%), respectively, and 10-year overall survival of 12.2% (95% CI, 7.3%-17.2%) vs 7.7% (95% CI, 3.6%-11.8%).
  
  
  CONCLUSIONS
  Among patients with macroscopic complete removal of pancreatic cancer, the use of adjuvant gemcitabine for 6 months compared with observation alone resulted in increased overall survival as well as disease-free survival. These findings provide strong support for the use of gemcitabine in this setting.
  
  
  BACKGROUND
  isrctn.org Identifier: ISRCTN34802808.
authors.affiliation: Medizinische Klinik mit Schwerpunkt Hämatologie, Onkologie und Tumorimmunologie, Charité-Universitätsmedizin Berlin, Berlin, Germany. helmut.oettle@charite.de
authors.forename: Helmut
authors.initials: H
authors.lastname: Oettle
authors.forename: Peter
authors.initials: P
authors.lastname: Neuhaus
authors.forename: Andreas
authors.initials: A
authors.lastname: Hochhaus
authors.forename: Jörg Thomas
authors.initials: JT
authors.lastname: Hartmann
authors.forename: Klaus
authors.initials: K
authors.lastname: Gellert
authors.forename: Karsten
authors.initials: K
authors.lastname: Ridwelski
authors.forename: Marco
authors.initials: M
authors.lastname: Niedergethmann
authors.forename: Carl
authors.initials: C
authors.lastname: Zülke
authors.forename: Jörg
authors.initials: J
authors.lastname: Fahlke
authors.forename: Michael B
authors.initials: MB
authors.lastname: Arning
authors.forename: Marianne
authors.initials: M
authors.lastname: Sinn
authors.forename: Axel
authors.initials: A
authors.lastname: Hinke
authors.forename: Hanno
authors.initials: H
authors.lastname: Riess
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000964:Antimetabolites, Antineoplastic / Q000009:adverse effects / Q000627:therapeutic use*; D017024:Chemotherapy, Adjuvant; D003841:Deoxycytidine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000601:surgery; D016019:Survival Analysis; D000093542:Gemcitabine
chemical_list: D000964:Antimetabolites, Antineoplastic; D003841:Deoxycytidine; D000093542:Gemcitabine